Starts 3-10 days before onset of menses and regresses/resolves at or shortly after (1-2 days) the onset of menstruation
Cyclic monthly episodes of urticaria most common; erythema multiforme, folliculitis, purpura, stomatitis, eczema, angioedema, papulovesicular eruptions, fixed drug eruptions, and vulvovaginal pruritis have also been reported
May also include other systems (airway angioedema, dyspnea, GI) and meet criteria for anaphylaxis
IgE-mediated, cell-mediated, and/or direct mast cell degranulation triggered by progesterone has been hypothesized
Detection of anti-progesterone IgG in some cases suggests an autoimmune basis
Most have previous exposure to exogenous progesterone
Catamenial anaphylaxis
Develops during menstruation
Similar to above
Endometrial-derived mediators such as PGF2-alpha or PGI2 (prostacyclin) may leak into the blood stream during menstruation
Similar syndromes have been reported (less frequently) suggesting estrogen sensitivity
Menstrual Cycle
Diagnosis
Rare; other possible etiologies should be fully considered, e.g. NSAID allergy
Proposed diagnostic criteria
Skin lesions related to the menstrual cycle
Positive response to intradermal testing with progesterone
Note that skin testing may not be positive in otherwise convincing cases
Symptomatic improvement after inhibiting progesterone secretion by suppressing ovulation
Skin Testing
Progesterone skin testing
Progesterone in sesame oil (50 mg/mL) with 10% benzyl alcohol for IM injection is easily available
Sesame proteins, benzyl alcohol, and oil may cause allergic or irritant reactions (acute and/or delayed onset)
Sesame oil with 10% benzyl alcohol may be obtained from compounding pharmacies for use as a negative control; healthy family member or staff may also serve as additional control
Progesterone aqueous solution not easily available but can be ordered from compounding pharmacy
Protocol (Castells)
SPT with progesterone 50 mg/mL (1:1)
ID with 1:10,000 (0.005 mg/mL), 1:1000 (0.05 mg/mL), 1:100 (0.5 mg/mL), and 1:10 (0.5 mg/mL) dilutions in normal saline
Use of full strength (1:1) ID skin testing has been reported by others
Ask patients to report/photograph delayed reactions
Skin testing with medroxyprogesterone also reported
Management
Acute symptomatic treatment for hypersensitivity reactions includes H1/H2 antihistamines, systemic steroids, epinephrine
Tends to be poorly respsonsive to antihistamines/steroids
Topical steroids reported to be effective for cutaneous lesions in some cases
Epinephrine auto-injector should be carried by patient if there is a history of anaphylaxis-like symptoms
Clinical Features
Autoimmune progesterone anaphylaxis
Menstrual Cycle
Diagnosis
Skin Testing
Management
References
Progesterone in Oil Injection - package insert